The major objective of this study is to identify genes which convey susceptibility to obesity and/or NIDDM in humans by studying the human genes which correspond to those that affect food intake, body weight and diabetes in animals (especially mice and rats). We will look for subtle variations in the genes that are related to differences in body fat mass and/or diabetes (adult onset, non-insulin dependent). Identification of these genes and their mechanisms of action in human subjects will help us to understand the causes of obesity and diabetes and indicate possible preventive or therapeutic measures. Our strategy is to establish a defined genetic resource consisting of nuclear families and individuals in which obesity and/or type II diabetes (NIDDM)are present. The study of inherited forms of obesity and diabetes in mice and rats, and physiological studies or energy metabolism in these and other animals have identified genes which may play a role in human obesity and diabetes. We can assess the possibility by examining the relationship between subtle variations in the candidate genes and the degree of obesity and/or presence of diabetes in individual and members of family groups. This study looks at such individuals from ten populations in the U.S. and Canada. Statistical techniques are used to identify regions of the genome and/or specific genes which may play a role in obesity and diabetes. We have already been able to determine a potential role for some of these candidate genes in human obesity.